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Updated: Aug 6, 2026

Development and Application of Rapamycin-regulated Tyrosine Phosphatases
Published on: September 6, 2024
MAPK-specific tyrosine phosphatases: new targets for drug discovery?
Alastair J Barr1, Stefan Knapp
1Structural Genomics Consortium, University of Oxford, Botnar Research Centre, Oxford, OX3 7LD, UK. alastair.barr@sgc.ox.ac.uk
Abstract:
Protein tyrosine phosphatases (PTPs) have key roles in a diverse range of cellular processes, and their dysregulation is associated with several human diseases. Many PTPs are recognized as potential drug targets; however, inhibitor development has focused only on a small number of enzymes, most notably PTP1B for type II diabetes and obesity, and MKP1 and CDC25 for cancer. The future challenge of selective-inhibitor development for PTPs will be significantly facilitated by the recent rapid progress in the structural biology of the 'PTPome'. In this article, we focus on the family of mitogen-activated protein kinase (MAPK)-specific tyrosine phosphatases--PTPN5 [also called striatal-enriched phosphatase (STEP)], PTPN7 (also called hematopoietic PTP) and PTPRR (also called PC12 PTP or STEP-like PTP)--and discuss approaches for achieving selectivity for the MAPK-PTPs at the molecular level using recently determined high-resolution X-ray crystal structures. We believe that the development of specific inhibitors would provide a valuable set of experimental pharmacological tools for investigating the physiological role of these phosphatases and exploring their emerging role in human disease.
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